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1.
Engyodontochones,Antibiotic Polyketides from the Marine Fungus Engyodontium album Strain LF069 下载免费PDF全文
Prof. Dr. Bin Wu Dr. Jutta Wiese Arlette Wenzel‐Storjohann Susan Malien Dr. Rolf Schmaljohann Prof. Dr. Johannes F. Imhoff 《Chemistry (Weinheim an der Bergstrasse, Germany)》2016,22(22):7452-7462
Six new ( 2 , 4 – 8 ) and two known polyketides with a basic structure of an anthraquinone‐xanthone were isolated from mycelia and culture broth of the fungus Engyodontium album strain LF069. The structures and relative configurations of these compounds were established by spectroscopic means, and their absolute configurations were defined mainly by comparison of quantum chemical TDDFT calculated and experimental ECD spectra. Compounds 2 and 4 – 8 were given the trivial names engyodontochone A ( 2 ) and B–F ( 4 – 8 ). Compounds 5 – 8 represent the first example of a 23,28 seco‐beticolin carbon skeleton. The relative and absolute configurations of two known substances JBIR‐97/98 ( 1 ) and JBIR‐99 ( 3 ) were determined for the first time. All isolated compounds were subjected to bioactivity assays. Compounds 1 – 4 exhibited inhibitory activity against methicillin‐resistant Staphylococcus aureus (MRSA) that was 10‐fold stronger than chloramphenicol. 相似文献
2.
Susan C. Scott Nicole M. Anders Ping He Avelina Hemingway Steven D. Gore Christine L. Hann Michelle A. Rudek 《Biomedical chromatography : BMC》2022,36(3):e5289
The Bcl-2 family small molecule inhibitor navitoclax is being clinically evaluated to treat multiple cancers including lymphoid malignancies and small cell lung cancer. A sensitive and reliable method was developed to quantitate navitoclax in human plasma using liquid chromatography with tandem mass spectrometry with which to perform detailed pharmacokinetic studies. Sample preparation involved protein precipitation using acetonitrile. Separation of navitoclax and the internal standard, navitoclax-d8, was achieved with a Waters Acquity UPLC BEH C18 column using isocratic flow over a 3 min total analytical run time. A SCIEX 4500 triple quadrupole mass spectrometer operated in positive electrospray ionization mode was used for the detection of navitoclax. The assay range was 5–5,000 ng/ml and proved to be accurate (89.5–104.9%) and precise (CV ≤ 11%). Long-term frozen plasma stability for navitoclax at −70°C was at least 43 months. The method was applied for the measurement of total plasma concentration of navitoclax in a patient receiving a 250 mg daily oral dose. 相似文献
3.
Brandon C. Presley Marisol S. Castaneto Barry K. Logan Susan A. Jansen-Varnum 《Biomedical chromatography : BMC》2020,34(9):e4884
FUB-AMB, an indazole carboxamide synthetic cannabinoid recreational drug, was one of the compounds most frequently reported to governmental agencies worldwide between 2016 and 2019. It has been implicated in intoxications and fatalities, posing a risk to public health. In the current study, FUB-AMB was incubated with human liver microsomes (HLM) to assess its metabolic fate and stability and to determine if its major ester hydrolysis metabolite (M1) was present in 12 authentic forensic human blood samples from driving under the influence of drug cases and postmortem investigations using UHPLC–MS/MS. FUB-AMB was rapidly metabolized in HLM, generating M1 that was stable through a 120-min incubation period, a finding that indicates a potential long detection window in human biological samples. M1 was identified in all blood samples, and no parent drug was detected. The authors propose that M1 is a reliable marker for inclusion in laboratory blood screens for FUB-AMB; this metabolite may be pharmacologically active like its precursor FUB-AMB. M1 frequently appears in samples in which the parent drug is undetectable and can point to the causative agent. The results suggest that it is imperative that synthetic cannabinoid laboratory assay panels include metabolites, especially known or potential pharmacologically active metabolites, particularly for compounds with short half-lives. 相似文献
4.
Electrolytic Macrocyclizations: Scalable Synthesis of a Diazonamide‐Based Drug Development Candidate 下载免费PDF全文
Dr. Hui Ding Patrick L. DeRoy Christian Perreault Dr. Alexandre Larivée Dr. Arshad Siddiqui Dr. Charles G. Caldwell Susan Harran Prof. Dr. Patrick G. Harran 《Angewandte Chemie (International ed. in English)》2015,54(16):4818-4822
An electrochemical method to synthesize the core macrolactam of diazonamides is described. Large ring‐forming dehydrogenation is initiated by anodic oxidation at a graphite surface. The reaction requires no tailoring of the substrate and occurs at ambient temperature in aqueous DMF in an undivided cell open to air. This unique chemistry has enabled a concise, scalable preparation of DZ‐2384; a refined analog of diazonamide A slated for clinical development as a cancer therapeutic. 相似文献
5.
Corrigendum: Crowdsourcing Natural Products Discovery to Access Uncharted Dimensions of Fungal Metabolite Diversity 下载免费PDF全文
6.
Frontispiece: Reversal of a Single Base‐Pair Step Controls Guanine Photo‐Oxidation by an Intercalating Ruthenium(II) Dipyridophenazine Complex 下载免费PDF全文
7.
In this work we present a novel approach for the identification of plant metabolites using ultrahigh performance liquid chromatography coupled to accurate mass time-of-flight mass spectrometry. The workflow involves developing an in-house compound database consisting of exact masses of previously identified as well as putative compounds. The database is used to screen accurate mass spectrometry (MS) data to identify possible compound matches. Subsequent tandem MS data is acquired for possible matches and used for structural elucidation. The methodology is applied to profile monoterpene glycosides in Vitis vinifera cv. Muscat of Alexandria grape berries over three developmental stages. Monoterpenes are a subclass of terpenes, the largest class of plant secondary metabolites, and are found in two major forms in the plant, “bound” to one or more sugar moieties or “free” of said sugar moieties. In the free form, monoterpenes are noted for their fragrance and play important roles in plant defense and as attractants for pollinators. However, glycoconjugation renders these compounds odorless, and it is this form that the plant uses for monoterpene storage. In order to gain insight into monoterpene biochemistry and their fate in the plant an analysis of intact glycosides is essential. Eighteen monoterpene glycosides were identified including a monoterpene trisaccharide glycoside, which is tentatively identified here for this first time in any plant. Additionally, while previous studies have identified monoterpene malonylated glucosides in other grapevine tissue, we tentatively identify them for the first time in grape berries. This analytical approach can be readily applied to other plants and the workflow approach can also be used for other classes of compounds. This approach, in general, provides researchers with data to support the identification of putative compounds, which is especially useful when no standard is available. 相似文献
8.
Enhanced‐fluidity liquid chromatography using mixed‐mode hydrophilic interaction liquid chromatography/strong cation‐exchange retention mechanisms 下载免费PDF全文
The potential of enhanced‐fluidity liquid chromatography, a subcritical chromatography technique, in mixed‐mode hydrophilic interaction/strong cation‐exchange separations is explored, using amino acids as analytes. The enhanced‐fluidity liquid mobile phases were prepared by adding liquefied CO2 to methanol/water mixtures, which increases the diffusivity and decreases the viscosity of the mixture. The addition of CO2 to methanol/water mixtures resulted in increased retention of the more polar amino acids. The “optimized” chromatographic performance (achieving baseline resolution of all amino acids in the shortest amount of time) of these methanol/water/CO2 mixtures was compared to traditional acetonitrile/water and methanol/water liquid chromatography mobile phases. Methanol/water/CO2 mixtures offered higher efficiencies and resolution of the ten amino acids relative to the methanol/water mobile phase, and decreased the required isocratic separation time by a factor of two relative to the acetonitrile/water mobile phase. Large differences in selectivity were also observed between the enhanced‐fluidity and traditional liquid mobile phases. A retention mechanism study was completed, that revealed the enhanced‐fluidity mobile phase separation was governed by a mixed‐mode retention mechanism of hydrophilic interaction/strong cation‐exchange. On the other hand, separations with acetonitrile/water and methanol/water mobile phases were strongly governed by only one retention mechanism, either hydrophilic interaction or strong cation exchange, respectively. 相似文献
9.
Novel Osmium‐based Coordination Complexes as Photosensitizers for Panchromatic Photodynamic Therapy 下载免费PDF全文
Savo Lazic Pavel Kaspler Ge Shi Susan Monro Tariq Sainuddin Sarah Forward Kamola Kasimova Robie Hennigar Arkady Mandel Sherri McFarland Lothar Lilge 《Photochemistry and photobiology》2017,93(5):1248-1258
Cancer remains a major global malaise requiring the advent of new, efficient and low‐cost treatments. Photodynamic therapy, which combines a photosensitizer and photons to produce cytotoxic reactive oxygen species, has been established as an effective cancer treatment but has yet to become mainstream. One of the main limitations has been the paucity of photosensitizers that are effective over a wide range of wavelengths, can exert their cytotoxic effects in hypoxia, are easily synthesized and produce few if any side effects. To address these shortfalls, three new osmium‐based photosensitizers (TLD1822, TLD1824 and TLD1829) were synthesized and their photophysical and photobiological attributes determined. These photosensitizers are panchromatic (i.e. black absorbers), activatable from 200 to 900 nm and have strong resistance to photobleaching. In vitro studies show photodynamic therapy efficacy with both red and near‐infrared light in normoxic and hypoxic conditions, which translated to good in vivo efficacy of TLD1829 in a subcutaneous murine colon cancer model. 相似文献
10.
Anton-Culver H Ziogas A Bowen D Finkelstein D Griffin C Hanson J Isaacs C Kasten-Sportes C Mineau G Nadkarni P Rimer B Schildkraut J Strong L Weber B Winn D Hiatt R Nayfield S 《Community genetics》2003,6(3):171-177
OBJECTIVE: The National Cancer Institute established the Cancer Genetics Network (CGN) to support collaborative investigations into the genetic basis of cancer susceptibility, explore mechanisms to integrate this new knowledge into medical practice, and identify ways of addressing the associated psychosocial, ethical, legal, and public health issues. SUBJECTS AND METHODS: The CGN has developed the complex infrastructure required to support the projects, including the establishment of guidelines and policies, uniform methods, standard questionnaires to be used by all of the centers, and a standard format for submission of data to the Informatics Center. Cancer patients and their family members have been invited to enroll and be included in a pool of potential study participants. The Information Technology Group is responsible for support of the design, implementation, and maintenance of the multicenter Network-wide research protocols. RESULTS: As of January 2004, the CGN contained data on 23,995 probands (participants) and 425,798 family members. As a resource for cancer genetic studies, the CGN has a large number of probands and first-degree relatives with and without cancer and with multiple ethnicities. Different study designs can be used including case-control, case-case, and family studies. CONCLUSIONS: The unique resources of the CGN are available for studies on cancer genetic susceptibility, translational research, and behavioral research. The CGN is now at a point where approved collaborators may have access to enrolled patients and their families for special studies, as well as to the clinical, environmental and family cancer history data banked in the Informatics Center. 相似文献